We plan to determine the local immune response in humans, first to naturally acquired enteric infections, and then to candidate vaccines. Our initial efforts will be in patients with cholera since this is a well defined "model" enterotoxigenic disease, with available vaccines. Next we will study patients with enterotoxigen E. coli diarrhea in both Bangladeshi persons hospitalized with severe diarrhea and in expatriates with travelers' diarrhea due to enterotoxigenic E. coli. We have recently developed methods which now make possible the quantitation of local antibodies using intestinal lavage specimens as well as saliva and breast milk in immunoglobulin class specific elisa assays for antitoxic and antibacterial antibodies. In addition we will use antitoxin neutralization assays (Y1 adrenal cell), vibriocidal assays, and are developing a microtiter complement independent vibrio antimotility assay. The methodology being developed for assessing the local immune response is crucial in the development of vaccines which will act by stimulating the local immune system. The application of the methodology first to naturally occurring disease is appropriate since this response can then serve as a yardstick against which to measure a vaccine response.